US-12625136-B2 - Sensor device

US12625136B2US 12625136 B2US12625136 B2US 12625136B2US-12625136-B2

Abstract

A device ( 1 ) for sensing an analyte, the device ( 1 ) comprises at least a sample inlet ( 10 ) for receiving a sample, affinity probes ( 111 ) selected to have a preferential binding to the analyte, a transducer ( 11 ) sensitive to a characteristic of the analyte and/or a label attached to the analyte, the transducer not being a FET transducer, and a desalting unit ( 13 ) for desalting the received sample.

Inventors

Willem Van Roy
Tim Stakenborg
Kris Covens

Assignees

IMEC VZW

Dates

Publication Date: 20260512
Application Date: 20211202
Priority Date: 20150630

Claims (12)

1 . A method for measuring a concentration of an analyte in a biological sample, the method comprising: receiving a biological sample; coupling the sample to affinity probes and a transducer; desalting the sample, wherein desalting the sample comprises performing electrodialysis on the affinity probes and the transducer; measuring at least one signal of the sample by means of an affinity-based sensing device based on the affinity probes and the transducer, the transducer not being a Field Effect Transistor transducer; and determining the concentration of the analyte in the sample using the at least one signal.
2 . The method according to claim 1 , wherein desalting the sample comprises bringing the sample to an ionic strength ranging from 10 nM to 150 mM.
3 . The method according to claim 1 , wherein desalting the sample and measuring the at least one signal of the sample are performed simultaneously.
4 . The method according to claim 1 , wherein the method further comprises a step of comparing the at least one signal to a reference signal obtained with a standard solution.
5 . The method according to claim 1 , wherein measuring the at least one signal of the sample is performed over time to obtain a measurement curve.
6 . The method according to claim 5 , further comprising determining a slope of the measurement curve.
7 . The method according to claim 1 , wherein performing electrodialysis comprises using at least two ion-selective membranes to reduce an ionic strength of the sample.
8 . The method according to claim 1 , wherein desalting the sample comprises bringing the sample to an ionic strength ranging from 10 mM to 150 mM.
9 . The method according to claim 1 , wherein the affinity-based sensing device comprises: at least a sample inlet for receiving the sample; the affinity probes, wherein the affinity probes are selected so as to have a preferential binding to the analyte; the transducer, wherein the transducer is sensitive to a characteristic of the analyte and/or a label attached to the analyte and adapted to convert an interaction of the analyte with the affinity probes into a readout signal, the transducer not being a Field Effect Transistor transducer; and a desalting unit for desalting the received sample so as to reduce a response time and/or increase the signal of the transducer.
10 . The method according to claim 1 , wherein the step of desalting the sample increases association kinetics of a hybridization reaction by at least an order of magnitude.
11 . The method according to claim 1 , wherein desalting the sample comprises using a desalting unit, wherein the desalting unit is integrated on a same substrate as the transducer.
12 . The method according to claim 1 , wherein the transducer comprises an optical transducer or an electrical transducer.

Description

The present application is a divisional of U.S. application Ser. No. 15/577,076, filed Nov. 27, 2017, which is a section 371 U.S. patent application claiming priority to PCT/EP2016/065449, filed Jun. 30, 2016, which claims priority from EP Application Serial No. 15174417.4, filed Jun. 30, 2015, the contents of these applications which are hereby incorporated by reference. TECHNICAL FIELD OF THE INVENTION The present invention relates to a device for sensing an analyte and to a method for measuring the presence and/or concentration of an analyte in a sample. In particular embodiments, the present invention may relate to a biosensor device. BACKGROUND OF THE INVENTION Affinity-based sensors are devices for sensing and detecting analytes in a sample, for instance in a liquid sample. Such sensors may operate on the basis of electrical, electrochemical, chemical, optical, magnetic, electromagnetic, mechanical, and/or acoustic detection principles. The detection of analytes in the sample is performed through interaction and reaction between specified reactants and the analytes in the sample. In particular in an affinity-based biosensor, the detection is based on the formation of a complex (hybridisation) between at least two entities, i.e. the analyte and a receptor or capture probe which may be immobilized on or in a substrate. The complex formation between the analyte and the capture probe leads to a signal that is measurable by a signal measurement unit. In order to make the binding detectable, in particular embodiments, a label element may be attached to the analyte. In alternative embodiments, however, detection may be based on a label-free operation. Real time sensing of biomolecules as a particular type of analytes, is particularly useful in many applications such as disease diagnosis or food safety, for example. Unfortunately, the response time of a biosensor device is often slow. This response time depends on a huge number of parameters such as, among other, the concentration of the analyte, the diffusion of the analyte, the kinetics of the hybridisation reaction and the stability of the obtained complex. For biosensors, the response times can vary from a few seconds to hours or more. It is generally admitted that in point-of-care (POC) or point-of-need applications, response time must be no longer than about 10 minutes. Moreover, the Limits of Detection (LOD) of existing biosensors can become higher (worse) if the various incubation times are reduced below their recommended values. There is therefore still a need to dispose of a device having short response time in the detection of the presence and/or in the measurement of concentrations of analyte and, preferably, having low limit of detection values. Furthermore, the methods implemented at present in devices for sensing an analyte, for instance in biosensors, need to be improved in order to decrease the response time. SUMMARY OF THE INVENTION It is an object of embodiments of the present invention to provide a device for sensing an analyte, for instance a biosensor, having a rapid response time for the detection of the presence and/or for the determination of the concentration of the analyte in a sample. Alternatively or additionally, the device according to embodiments of the present invention may present an increased signal of the transducer, thereby allowing to detect the analyte more rapidly and/or at smaller concentrations. It is also an object of the present invention to provide a method to be implemented in a device for measuring an analyte, for instance in a biosensor, the method leading to fast response times for the detection of the presence and/or for the determination of the concentration of the analyte in a sample. In a first aspect, the present invention relates to a device for sensing an analyte, for instance a biosensor, the device comprising at least a sample inlet for receiving a sample, in particular for instance a liquid sample, affinity probes selected to have a preferential binding to the analyte, and a transducer sensitive to a characteristic of the analyte and/or a label attached to the analyte, and adapted to convert an interaction of the analyte with the affinity probes into a readout signal, the transducer not being a field-effect transducer, such as a field-effect transistor (FET), and a desalting unit for desalting the received sample so as to increase the binding rate between the affinity probes and the analyte and consequently to reduce the response time and/or increase the signal of the transducer. The inventors have surprisingly found that the presence of a desalting unit in a device for sensing an analyte, for instance a biosensor, permits to obtain a faster response from the device. The measurable signal (the output signal) increases faster as compared to a similar device without the desalting unit. Moreover, by using a desalting unit in a device for sensing an analyte, the limit of detection is decreased (=improved)